Mild irritant prevents ethanol-induced gastric mucosal microcirculatory disturbances through actions of calcitonin gene-related peptide and PGI2 in rats

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2004-01, Vol.286 (1), p.G68
• Main Authors: Saeki, Takeo, Ohno, Takashi, Kamata, Kazuhisa, Arai, Katsuharu, Mizuguchi, Sumito, Katori, Makoto, Saigenji, Katsunori, Majima, Masataka
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Calcitonin Gene-Related Peptide - pharmacology; Calcitonin Gene-Related Peptide - physiology; Central Nervous System Depressants - antagonists & inhibitors; Central Nervous System Depressants - toxicity; Epoprostenol - analogs & derivatives; Epoprostenol - pharmacology; Epoprostenol - physiology; Ethanol - antagonists & inhibitors; Ethanol - toxicity; Gastric Mucosa - blood supply; Gastric Mucosa - drug effects; Gastric Mucosa - pathology; Indomethacin - pharmacology; Irritants - pharmacology; Male; Microcirculation - drug effects; Microcirculation - pathology; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Regional Blood Flow - drug effects; Sodium Chloride - pharmacology; Venules - drug effects
• ISSN: 0193-1857

Pretreatment with a mild irritant such as 1 M NaCl prevented ethanol-induced mucosal injury, which was abolished by indomethacin, suggesting involvement of endogenous PGs. With the use of intravital microscopy, we investigated the mechanism in microcirculation whereby a mild irritant prevents ethanol-induced mucosal injury. Microcirculation of the basal part of gastric mucosa in anesthetized rats was observed through a window with transillumination. Diameters of arterioles, collecting venules, and venules were measured with an electric microscaler. One molar NaCl alone caused dilation of arterioles and constrictions of collecting venules and venules, which were inhibited by indomethacin. Ethanol (50%) applied to mucosa constricted collecting venules and venules but dilated arterioles. Constriction of collecting venules resulted in mucosal congestion. Pretreatment with 1 M NaCl inhibited ethanol-induced constrictions of collecting venules and venules, and administration of indomethacin or a calcitonin gene-related peptide (CGRP) antagonist, CGRP-(8-37), abolished elimination of constrictions. Topical application (1 nM-10 microM) of PGE2 or beraprost sodium (a PGI2 analog) to microvasculature markedly and dose-dependently dilated arterioles, whereas that of PGE2, but not beraprost, slightly constricted collecting venules. Pretreatment of microvasculature with a nonvasoactive concentration of PGE2 (100 nM) or beraprost (1 nM) completely inhibited ethanol-induced constriction of collecting venules. The inhibitory effect of beraprost but not of PGE2 was abolished by CGRP-(8-37). Present results suggest that the mechanism whereby 1 M NaCl prevents ethanol-induced injury is elimination of constrictions of collecting venules and venules by CGRP whose release may be enhanced by PGI2 but not by PGE2.